Modulation of T cell signaling threshold and T cell sensitivity to antigens

US7803784B2 · kind B2 · utility

Assignee

• The Board of Trustees of the Leland Stanford Junior University · US

Inventors

• Qi Li · Mountain View, US
• Chang-Zheng Chen · Stanford, US
• Mark M. Davis · Mountain View, US
• Jacqueline Chau · Santa Clara, US

Key dates

• Filing date: Oct 24, 2007
• Grant date: Sep 28, 2010
• Expiry date: Oct 24, 2027

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2800/24
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

MicroRNAs (miRNAs) are a diverse and abundant class of ˜22-nucleotide (nt) endogenous regulatory RNAs that play a variety of roles in animal cells by controlling gene expression at the posttranscriptional level. Increased miR-181a expression in mature T cells is shown to cause a marked increase in T cell activation and augments T cell sensitivity to peptide antigens. Moreover, T cell blasts with higher miR-181a expression become reactive to antagonists. The effects of miR-181a on antigen discrimination are in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway, including PTPN22 and the dual specificity phosphatases DUSP5 and DUSP6. This results in a reduction in the TCR signaling threshold, thus quantitatively and qualitatively enhancing T cell sensitivity to antigens.